The effect of COVID-19 vaccination status on all-cause mortality in patients hospitalised with COVID-19 in Hungary during the delta wave of the pandemic.

The high mortality of patients with coronavirus disease 2019 (COVID-19) is effectively reduced by vaccination. However, the effect of vaccination on mortality among hospitalised patients is under-researched. Thus, we investigated the effect of a full primary or an additional booster vaccination on in-hospital mortality among patients hospitalised with COVID-19 during the delta wave of the pandemic. This retrospective cohort included all patients (n = 430) admitted with COVID-19 at Semmelweis University Department of Medicine and Oncology in 01/OCT/2021-15/DEC/2021. Logistic regression models were built with COVID-19-associated in-hospital/30 day-mortality as outcome with hierarchical entry of predictors of vaccination, vaccination status, measures of disease severity, and chronic comorbidities. Deceased COVID-19 patients were older and presented more frequently with cardiac complications, chronic kidney disease, and active malignancy, as well as higher levels of inflammatory markers, serum creatinine, and lower albumin compared to surviving patients (all p < 0.05). However, the rates of vaccination were similar (52-55%) in both groups. Based on the fully adjusted model, there was a linear decrease of mortality from no/incomplete vaccination (ref) through full primary (OR 0.69, 95% CI: 0.39-1.23) to booster vaccination (OR 0.31, 95% CI 0.13-0.72, p = 0.006). Although unadjusted mortality was similar among vaccinated and unvaccinated patients, this was explained by differences in comorbidities and disease severity. In adjusted models, a full primary and especially a booster vaccination improved survival of patients hospitalised with COVID-19 during the delta wave of the pandemic. Our findings may improve the quality of patient provider discussions at the time of admission.

Pathogenesis, clinical characteristics, diagnostics and treatment of bacterial foodborne diseases / Élelmiszer eredetu bakteriális megbetegedések patogenezise, klinikai jellegzetességei, diagnosztikája és kezelése.

Összefoglaló. Az élelmiszer-eredetu megbetegedések igen gyakoriak, bár pontos adatok nem állnak rendelkezésre, mivel az enyhe, gyorsan múló gastrointestinalis tünetekkel a betegek nem fordulnak orvoshoz, vagy nem történik diagnosztikus vizsgálat. Az amerikai Járványügyi és Betegségmegelozési Központ (CDC) adatai szerint az USA-ban évente 6 lakosból 1 esik át élelmiszer okozta tüneteken. Az ételintoxikációk során a baktérium által termelt toxinok okozzák a tüneteket, közülük a leggyakoribb a Clostridium perfringens, a Staphylococcus aureus és a Bacillus cereus okozta, élelmiszer-eredetu intoxikáció. A nem megfeleloen tárolt vagy hokezelt élelmiszerekben - beleértve a S. aureus által szennyezett anyatejet - ezen baktériumok életképesek maradnak, elszaporodnak, és toxint termelhetnek, illetve toxinjaik megorzik megbetegítoképességüket. Az étel elfogyasztása után 3-12 órával hányást, hasmenést okoznak. A tünetek többnyire 24 órán belül megszunnek. A Clostridium botulinum súlyos neurológiai tünetei miatt emelkedik ki a többi toxikoinfekció sorából. C. botulinum okozta tünetekre felnotteknél házi készítésu konzervek és húskészítmények elfogyasztása után jelentkezo gastrointestinalis vagy neurológiai tünetek esetén kell gondolnunk. A Clostridioides difficile szintén a toxinjai révén okoz súlyos, életveszélyes megbetegedést, továbbá az esetek 20-30%-ában számolnunk kell az infekció relapsusával. Növekvo gyakorisága miatt ismernünk érdemes a laboratóriumi és klinikai diagnosztika részleteit és a legmodernebb kezelési lehetoségeket, úgymint megfelelo mintavétel, mintatárolás és -szállítás, tenyésztés, toxinkimutatás, helyes tüneti kezelés, antibiotikumkombinációk, széklettranszplantáció és monoklonálisantitest-kezelés. Orv Hetil. 2020; 161(48): 2019-2028. Summary. Foodborne diseases are quite common, however, accurate data are not available because patients do not visit doctors with mild, rapidly resolving symptoms and diagnostic tests are not performed. The Centers of Disease Control and Prevention (CDC) estimates that, in the USA, 1 in 6 citizens gets food poisoning yearly. Symptoms of intoxication are due to the toxins produced by bacteria, mostly by Clostridium perfringens, Staphylococcus aureus and Bacillus cereus. These bacteria can survive in not properly stored or heated food, including S. aureus contaminated breastmilk. They can multiply and produce toxins causing intoxications. The gastrointestinal symptoms start 3-12 hours after consumption of the contaminated food and resolve in 24 hours. Clostridium botulinum causes severe neurological symptoms that should be suspected after consumption of home-made cans, smoked hams and sausages. The disease caused by Clostridioides difficile is not a foodborne one, but C. difficile causes severe infection via its toxins. Another problem is that C. difficile infection recurs in 20-30% of cases. Due to the increasing incidence of foodborne diseases, it is worth to learn the precise clinical and laboratory diagnostic algorithms including sampling, storage and transportation of samples, cultivation of bacteria and differential diagnosis of these diseases, furthermore the most up-to-date symptomatic and causative treatment options like antibiotic combinations, stool transplantation and monoclonal antibodies. Orv Hetil. 2020; 161(48): 2019-2028.

High prevalence of group B streptococcus ST17 hypervirulent clone among non-pregnant patients from a Hungarian venereology clinic.

BACKGROUND: Although Streptococcus agalactiae is the leading causative agent of neonatal sepsis and meningitis, recently it is increasingly isolated from non-pregnant adults. The relation between its presence in the genitourinary tract and manifested clinical symptoms of STD patients remains an open question. In this study, a complex epidemiological investigation of GBS isolates from a venerology clinic was performed. METHODS: Ninety-six GBS isolates were serotyped and their genetic relatedness determined by PFGE. MLST was also performed for a subset of 20 isolates. The antibiotic susceptibility was tested with agar dilution. Surface proteins and the ST-17 hypervirulent clone was detected by PCR. RESULTS: The serotype prevalence was the following: V (29.2%), III (27.1%), Ia (22.9%), IV (10.4%), II (5.2%) and Ib (4.2%). A strong association was demonstrated between surface protein genes and serotypes. All isolates were fully susceptible to penicillin, but erythromycin and clindamycin resistance was high (41.7 and 35.4%, respectively), and 8 phenotypically macrolide sensitive isolates carried the ermB gene. 21.9% of all strains belonged to the hypervirulent ST17 clone, most being of serotype III and all were rib +. We found a few serotype IV isolates belonging to several STs and one serotype V/ST110 strain, containing a 44-bp deletion in the atr allele. CONCLUSIONS: The presence of silent ermB genes is of worry, as their expression upon macrolide exposure could lead to unforeseen therapeutic failure, while clindamycin is used for intrapartum antibiotic prophylaxis, in case of penicillin allergy. The other alarming result is the high prevalence of ST17 among these strains from STD patients, who could be sources of further infections. This is the first report from Hungary providing both serotyping and genotyping data of GBS isolates. These results could be helpful for vaccine production as the major vaccine candidates are capsular antigens or surface proteins.

Synthesis and antibacterial evaluation of some teicoplanin pseudoaglycon derivatives containing alkyl- and arylthiosubstituted maleimides.

Bis-alkylthio maleimido derivatives have been prepared from teicoplanin pseudoaglycon by reaction of its primary amino group with N-ethoxycarbonyl bis-alkylthiomaleimides. Some of the new derivatives displayed excellent antibacterial activity against resistant bacteria.

A few atoms make the difference: synthetic, CD, NMR and computational studies on antiviral and antibacterial activities of glycopeptide antibiotic aglycon derivatives.

Despite the close structural similarity between the heptapeptide cores of the glycopeptide antibiotics teicoplanin and ristocetin, synthetically modified derivatives of their aglycons show significantly different antibacterial and antiviral properties. The teicoplanin aglycon derivatives with one exception proved to be potent antibacterials but they did not exhibit anti-influenza virus activity. In contrast, the aglycoristocetin derivatives generally showed high anti-influenza virus activity and possessed moderate antibacterial activity. A systematic structure-activity relationship study has been carried out on ristocetin and teicoplanin aglycon derivatives, to explore which structural differences are responsible for these markedly different biological activities. According to electronic circular dichroism and in silico conformational studies, it was found that the differences in anti-influenza virus activity are mainly determined by the conformation of the heptapeptide core of the antibiotics controlled by the presence or absence of chloro substituents. Knowledge of the bioactive conformation will help to design new analogs with improved anti-influenza virus activity. For the teicoplanin derivatives, it was shown that derivatization to improve the antiviral efficacy was accompanied by a significant decrease in antibacterial activity.

Semisynthetic teicoplanin derivatives as new influenza virus binding inhibitors: synthesis and antiviral studies.

In order to obtain new, cluster-forming antibiotic compounds, teicoplanin pseudoaglycone derivatives containing two lipophilic n-octyl chains have been synthesized. The compounds proved to be poor antibacterials, but, surprisingly, they exhibited potent anti-influenza virus activity against influenza A strains. This antiviral action was related to inhibition of the binding interaction between the virus and the host cell. Related analogs bearing methyl substituents in lieu of the octyl chains, displayed no anti-influenza virus activity. Hence, an interaction between the active, dually n-octylated compounds and the lipid bilayer of the host cell can be postulated, to explain the observed inhibition of influenza virus attachment.

Syphilis and HIV coinfection - Hungarian Sexually Transmitted Infection Centre Experience between 2005 and 2013.

BACKGROUND: STIs like HIV and syphilis are acquired as comorbidities by high risk populations and may influence their original course and prognosis. METHODS: Between January of 2005 and 2013 data of syphilis and HIV patients were collected at the Department of Dermatology of Semmelweis University, Budapest. Diagnostic procedures included clinical analysis and screening of serum samples for Treponema pallidum and HIV antibodies. RESULTS: A total of 1,401 new syphilitic and 338 new HIV infections were diagnosed. In syphilis patients 86.58% had monoinfection,7.92% already had an HIV infection and 5.5% had acquired syphilis and HIV infection simultaneously, so 22.78% of the new HIV patients acquired the infection with syphilis together. Male gender, MSM (men who had sex with men) orientation and positive past venerological history were dominant in all groups. Most patients were diagnosed in a latent infectious stage based on the result of a serological check-up. Secondary stage and neurosyphilis were more common in coinfections. CONCLUSION: (i) male gender, MSM orientation, and positive venerological history are risk factors for acquiring new STIs, (ii) clinical course were different in HIV infected patients, (iii) but their timely and regular check-ups resulted in earlier diagnosis of syphilis, suggesting the necessity for frequent screening.

Synthesis of fluorescent ristocetin aglycon derivatives with remarkable antibacterial and antiviral activities.

Isoindole and benzoisoindole derivatives of ristocetin aglycon have been prepared by reaction with o-phthalaldehyde or naphthalene-2,3-dialdehyde and various thiols. The new compounds exhibited potent antibacterial and anti-influenza virus activity. The cluster forming and fluorescent properties of the aglycon derivatives were also studied.

Synthesis of isoindole and benzoisoindole derivatives of teicoplanin pseudoaglycon with remarkable antibacterial and antiviral activities.

The primary amino function of teicoplanin pseudoaglycon has been transformed into arylthioisoindole or benzoisoindole and glycosylthioisoindole derivatives, in a reaction with o-phthalaldehyde or naphtalene-2,3-dicarbaldehyde and various thiols. All of the obtained semisynthetic antibiotics exhibited potent antibacterial activities against Gram-positive bacteria in the ng per ml concentration range. A few of them showed antiviral activity, in particular against influenza virus.

Nano-sized clusters of a teicoplanin ψ-aglycon-fullerene conjugate. Synthesis, antibacterial activity and aggregation studies.

Glycopeptide antibiotic derivative teicoplanin ψ-aglycone has been bound covalently to a fullerenopyrrolidine derivative using azide-alkyne 1,3-dipolar cycloaddition reaction. The aggregation of the antibiotic-fullerene conjugate in aqueous solution has been studied. The conjugate exhibited antibacterial activity against enterococci resistant to teicoplanin.

Synthesis of osteotropic hydroxybisphosphonate derivatives of fluoroquinolone antibacterials.

1-Hydroxybisphosphonate derivatives of ciprofloxacin, gatifloxacin and moxifloxacin have been synthesized using Cu(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction. The 1,2,3-triazol linked hydroxybisphosphonate derivative of ciprofloxacin exhibited antibacterial activity comparable to the parent antibiotic and all fluoroquinolone-bisphosphonates displayed osteotropic properties in a bone model.

[Frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples of sexually active individuals]. / Az Ureaplasma urealyticum és a Mycoplasma hominis antibiotikum-érzékenysége és gyakorisága szexuálisan aktív egyének genitális mintáiban.

UNLABELLED: Ureaplasma urealyticum and Mycoplasma hominis have important role among the causative agents of sexually transmitted diseases. AIM: The aim of the study was to determine the frequency and antibiotic resistance of Ureaplasma urealyticum and Mycoplasma hominis in genital samples obtained from patients examined in the Sexually Transmitted Diseases Centre of the Department of Dermatology, Venerology and Dermatooncology, Semmelweis University, Budapest between May 1, 2008 and July 31, 2010. PATIENTS AND METHODS: Samples were taken from the urethra in men and from the cervix and urethra in women by universal swab (Biolab®) into Urea-Myco DUO kit (Bio-Rad®) and were incubated for 48 hours at 37 C°. Antibiotic sensitivity of positive samples was determined in U9 bouillon using SIR Mycoplasma kit (Bio-Rad®). RESULTS: Samples for 4154 patients aged 16-60 years were examined. In 247/4154 samples (6%) U. urealyticum and in 26/4154 samples (0.63%) M. hominis was isolated from the genital tract. Most U. urealyticum and M. hominis strains (75% and 77%, respectively) were cultured from cervix, while the remaining 25%, and 23% from the male and female urethra, respectively. U. urealyticum and M. hominis were most commonly detected in patients aged between 21 and 40 years. The majority of U. urealyticum strains were sensitive to tetracycline (94%), doxycycline (95%), azithromycin (88%) and josamycin (90%), but were resistant to ofloxacin (21%), erythromycin (85%) and clindamycin (79%). Seventy-seven percent of the U. urealyticum strains were simultaneously resistant to erythromycin and clindamycin, suggesting that ex iuvantibus therapies may select cross-resistant strains to both antibiotics. The resistance of M. hominis to clindamycin, doxycycline, ofloxacin and tetracycline varied between 4% and 12 %. CONCLUSIONS: Because none of the strains was sensitive to all examined antibiotics, the antibiotic sensitivity of U. urealyticum and M. hominis strains should be determined. The high rate of ofloxacin, erythromycin and clindamycin resistance should be considered in the therapy of U. urealyticum infections in Hungary. This is the first such a clinical microbiological study in this topic in Hungary.

Broad-spectrum antimicrobial efficacy of peptide A3-APO in mouse models of multidrug-resistant wound and lung infections cannot be explained by in vitro activity against the pathogens involved.

Although the designer proline-rich antimicrobial peptide A3-APO has only modest activity against Escherichia coli and Acinetobacter baumannii in vitro, in mouse models of systemic and wound infections it shows superior efficacy compared with conventional antibiotics. In this study, the efficacy of A3-APO in several additional mouse models was investigated, including Staphylococcus aureus wound infection, mixed Klebsiella pneumoniae-A. baumannii-Proteus mirabilis wound infection and K. pneumoniae lung infection, mimicking blast wound infections, foot ulcers and ventilator-induced nosocomial infections, respectively. Whilst the peptide practically did not kill the strains in vitro, when administered intramuscularly or as an aerosol it significantly improved mouse survival and reduced bacterial counts at the infection site and in blood. In the lung infection study, the blood bacterial counts following A3-APO treatment were as low as after treatment with colistin and were lower than after treatment with imipenem or amikacin. The wounds of treated animals, unlike their untreated counterparts, lacked pus and signs of inflammation. In human peripheral blood mononuclear cells, A3-APO upregulated the expression of the anti-inflammatory cytokines interleukin-4 and interleukin-10 by four- to six-fold. One of the mechanisms mediating the in vivo protective effects might be the prevention of inflammation around bacterial infiltration.

The effect of systematic structural modifications on the antibacterial activity of novel oxazolidinones.

A novel series of tetraethylene glycol (TEG) triazolyl and squaramide containing oxazolidinones were synthesized and tested for their antibacterial activity against a selected panel of Gram-positive and Gram-negative bacteria. The 4-TEG-triazolyl derivatives were prepared by 'click reaction'. The introduction of the TEG and squaramide groups did not favor antibacterial activity. The three nucleoside-containing oxazolidinones were also prepared by 'click' methodology resulted in weak antibacterial activity.

Intramuscularly administered peptide A3-APO is effective against carbapenem-resistant Acinetobacter baumannii in mouse models of systemic infections.

Most antibacterial peptides exhibit low therapeutic indices in vivo. Peptide A3-APO was shown to exhibit high potency against Escherichia coli bacteremia when added intraperitoneally. To extend the studies to systemic infections against multidrug-resistant organisms, we studied the efficacy of A3-APO in mouse models of carbapenem-resistant Acinetobacter baumannii infection. When administered either intravenously at 2.5 mg/kg or intramuscularly (im) at 5 mg/kg twice or three times to mice infected with a carbapenem-resistant A. baumannii strain, peptide A3-APO reduced the bacterial counts by at least two log10 units and increased the survival rate compared with untreated animals or mice treated with 40 mg/kg imipenem. Unlike after intraperitoneal or intravenous administration, A3-APO did not show toxic effects at 60 mg/kg dose im.

Genotypic and phenotypic characterisation of invasive Streptococcus pneumoniae isolates from Hungary, and coverage of the conjugate vaccines.

BACKGROUND AND AIMS: The 7-valent conjugate pneumococcal vaccine (Prevenar) was introduced as a recommended (but not yet obligatory) vaccine in Hungary in April 2009 and there was a sharp increase in the number of children vaccinated. Hence there is an urgent need for in-depth epidemiological data on invasive pneumococci before vaccination becomes widespread. Such a study has never been done before in Hungary. METHODS: 144 pneumococcal isolates, obtained from invasive infections or pneumonia, were collected from eight Hungarian diagnostic laboratories between 2000 and 2008. After confirmation of species identity, their susceptibilities to nine antibiotics were determined by Etest and agar dilution method. The serotypes and pulsed-field gel electrophoresis genotypes of the strains were also determined. RESULTS: In this cohort, most of the isolates were from patients at the extreme of life. Only 1.4% of the strains were resistant to penicillin, but nearly 40% were resistant to erythromycin (mainly due to erm(B) gene). Higher incidences of resistance were found in the very young and very old. The most prevalent serotypes in the cohort in descending order were 14, 6A, 6, 6B, 23F, 3, 19F and 11A. CONCLUSIONS: Results showed a similar but not identical profile to previously examined strains causing pulmonary infections in Hungary. The serotypes could be correlated to patient groups. Furthermore, there were examples of serotype switching in strains showing identical genotype but different serotype. The study also shows a good coverage by the conjugate vaccines over the invasive pneumococcal strains in Hungary based on the detected serotypes.

Preclinical advantages of intramuscularly administered peptide A3-APO over existing therapies in Acinetobacter baumannii wound infections.

OBJECTIVES: The designer antibacterial peptide A3-APO is efficacious in mouse models of Escherichia coli and Acinetobacter baumannii systemic infections. Here we compare the efficacy of the peptide with that of imipenem and colistin in A. baumannii wound infections after burn injury. METHODS: CD-1 mice were inflicted with burn wounds and different inocula of A. baumannii, isolated from an injured soldier, were placed into the wound sites. The antibiotics were given intramuscularly (im) one to five times. Available free peptide in the blood and the systemic toxicity of colistin and A3-APO were studied in healthy mice. RESULTS: While toxicity of colistin was observed at 25 mg/kg bolus drug administration, the lowest toxic dose of A3-APO was 75 mg/kg. In the A. baumannii blast injury models, 5 mg/kg A3-APO improved survival and reduced bacterial counts in the blood as well as in the wounds and improved wound appearance significantly better than any other antibiotic treatment. The free peptide concentration in the blood did not reach 1 µg/mL. CONCLUSIONS: Peptide A3-APO, with an intramuscular therapeutic index of 15, is more efficacious and less toxic than any existing burn injury infection therapy modality against multidrug-resistant Gram-negative pathogens. A3-APO administered by the im route probably binds to a biopolymer that promotes the peptide's biodistribution.

[Cost/benefit calculations of meticillin-resistant Staphylococcus aureus screening methods and their practical importance]. / A methicillinrezisztens Staphylococcus aureus -szurés költséghatékonysági vizsgálata és gyakorlati jelentosége.

Nosocomial infections are the main cause of extra charges in health care and they relate to patient safety, as well. About 30 percent of healthcare-associated infections can be prevented effectively with infection control and adequate screening methods. Currently, meticillin-resistant Staphylococcus aureus is the main nosocomial pathogen. Protective measures against this bacterium are well known, therefore it was selected for our present cost /benefit analysis. We have calculated the costs of the epidemic caused by methicillin-resistant Staphylococcus aureus at the Aladar Petz County Teaching Hospital, Gyor, in a two-year period, and also calculated the costs of the screening method. We compared our results with the published data. Screening methods are much less expensive than to cure the patient of a nosocomial infection. Thus, primary prevention has essential importance.

Click reaction synthesis of carbohydrate derivatives from ristocetin aglycon with antibacterial and antiviral activity.

New sugar derivatives of ristocetin were prepared by copper-catalyzed 1,3-dipolar cycloaddition reaction using azido-ristocetin aglycon and various propargyl glycosides. Some of them were found to be active against gram-positive bacteria and showed favorable antiviral activity against the H1N1 subtype of influenza A virus.

The designer proline-rich antibacterial peptide A3-APO is effective against systemic Escherichia coli infections in different mouse models.

Antimicrobial peptides are considered to be viable alternatives to conventional antibiotics. However, they rarely show systemic efficacy in animal models when added at non-toxic doses. The dimer A3-APO was designed to attack both the bacterial membrane and the Enterobacteriaceae-specific domain of the heat shock protein DnaK in order to reduce toxicity whilst maintaining activity. The peptide exhibited a minimal inhibitory concentration (MIC) range of 2-128 mg/L against 28 clinical Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium strains, with a median MIC of 30 mg/L. At this concentration, A3-APO was bactericidal to E. coli 5770, a fluoroquinolone-resistant extended-spectrum beta-lactamase-producing strain. The No Observed Adverse Effect Limit (NOAEL) at repeated intraperitoneal peptide administration was 20mg/kg. When administered at this dose three times starting immediately after E. coli Neumann infection, A3-APO cured 100% of mice in a standard bacteraemia model used by the pharmaceutical industry. In a more stringent assay, when treatment started after E. coli 5770 bacteraemia had already been established, three doses of 10mg/kg A3-APO prolonged early survival at a rate similar to that of imipenem and reduced the bacterial counts to base level. When the second assay was repeated in kidney clearance conditions resembling those in humans, 10mg/kg A3-APO was as efficacious as imipenem in the long-term. The increased in vivo efficacy compared with the in vitro bactericidal figures can potentially be explained by the generally observable immunostimulatory properties of antimicrobial peptides. Peptide A3-APO shows promising features as a member in our antibiotic arsenal against multidrug-resistant bacterial pathogens.